Lipoprotein lipase is a key enzyme in fat metabolism. Dietary fat accounts for as much as one-half of the daily caloric intake in normal man. The assimilation of both dietary and endogeneous triglycerides depends on the activity of this enzyme. Recent observations suggest that lipoprotein lipase is subject to fine metabolic and hormonal control. There appear to be major differences in the control of lipoprotein lipase within different tissues: Hormones stimulate enzyme activity in some tissues and depress it in others. In this way, regulation of the lipoprotein lipase system provides a finely modulated mechanism for directing triglyceride fatty acids to substrate-requiring tissues. We will study four aspects of the lipoprotein lipase system: 1) We will purify lipoprotein lipase from a mammalian source and raise antisera to it. The antisera will be used for immunological studies of enzyme distribution in tissues, lipoprotein lipase isoenzymes and other aspects of lipoprotein lipase physiology; 2) Studies of of plasma postheparin lipolytic activity and heparin metabolism will be carried out simultaneously in human volunteers; 3) We will investigate the effects of sex steroids on tissue lipoprotein lipase activity in experimental animals to clarify the importance of these substances to lipid transport and; 4) We will examine the effects of mucopolysaccharide-degrading enzymes on lipoprotein lipase structure and activity. The long-range objective of this project is to clarify the significance of the lipoprotein lipase pathway to human physiology and to the pathogenesis of atherosclerosis in man. BIBLIOGRAPHIC REFERENCES: Wilson, D.E., Jubiz, W., Flowers, C.M., Carlile, S.I., and Adolf, A.M.: Tissue lipoprotein lipase in the hyperthyroid rat. Atherosclerosis, 1977, in press. Brown, W.V., and Wilson, D.E.: Lipid and lipoproteins in diabetes mellitus. Adv. Modern Nutrition, 1977, in press.